The long-range goal is to generate a technology that will allow clinicians to prescribe an "ideal" vocal exercise (or rest) program that should optimize tissue healing for both acute and chronic phonotrauma. In the present series, we focus on the acute case. Short-term goals are (a) to establish a methodology to quantitatively characterize the patient's current inflammatory profile, and (b) to develop a hybrid aeromechanical/biological in silico model of complex systems that can ultimately identify regimens of voice use and rest that should optimize molecular/cellular profiles over time, given varying initial inflammatory states. Work from our laboratory has made good progress in addressing the first short-term goal. Specifically, we have developed an in vivo technology that appears to quantitatively characterize the current inflammatory status in the larynx. We have also completed preliminary work to address the second goal. We have developed preliminary aerodynamic, Agent-Based and Ordinary Differential Equation Models of vocal fold inflammation calibrated to human and animal data. In the present series, we propose to (1): establish a non-invasive methodology for estimating overall mechanical dose during phonation, and component metrics of phonatory mechanical dose (e.g., distance dose, energy dissipation dose and time dose) from high speed imaging data and aeromechanical modeling, for a range of vocal fold configurations; (2): identify mathematical relations between mechanical dose parameters, inflammatory state of the tissue and time-varying biological consequences in the tissue, up to 3 wk following acute phonotrauma; (3): develop a hybrid physical-biological model of vocal fold inflammation and treatment to identify phonation modalities that should optimize post-traumatic wound healing at 3 wk, for a range of acute phonotraumatic conditions, and (4): provide a preliminary test of the hybrid treatment models' ability to predict idealized treatment outcome in human subjects, and calibrate the model as needed iteratively to achieve a match between predicted and obtained outcomes. The hypothesis is that with this approach, a platform can be developed that will ultimately allow for the prescription of patient-specific treatments for acute phonotrauma that will optimize long-term healing, and that the final results will indicate that some forms of vocal exercise may facilitate biological recovery in the tissue, compared to voice rest, for some phonotraumatic conditions. [unreadable] [unreadable] [unreadable]